Identification

Name
Xylitol
Accession Number
DB11195  (EXPT03268, DB01904)
Type
Small Molecule
Groups
Experimental, Investigational
Description

Xylitol is a naturally occurring five-carbon sugar alcohol found in most plant material, including many fruits and vegetables. Xylitol-rich plant materials include birch and beechwood [1]. It is widely used as a sugar substitute and in "sugar-free" food products. The effects of xylitol on dental caries have been widely studied, and xylitol is added to some chewing gums and other oral care products to prevent tooth decay and dry mouth. Xylitol is a non-fermentable sugar alcohol by most plaque bacteria, indicating that it cannot be fermented into cariogenic acid end-products [4]. It works by inhibiting the growth of the microorganisms present in plaque and saliva after it accummulates intracellularly into the microorganism [4]. The recommended dose of xylitol for dental caries prevention is 6–10 g/day, and most adults can tolerate 40 g/day without adverse events [1].

Structure
Thumb
Synonyms
  • D-Xylitol
External IDs
E-967 / E967 / INS NO.967 / INS-967
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Claon (toothpaste)Paste, dentifrice0.07 g/100gDentalMbg Inc (Korea Institute of Science Development)2017-07-112018-07-11Us
MedisupiaPaste, dentifrice0.07 g/100gDentalMbg Inc (Korea Institute of Science Development)2016-07-112016-07-11Us
Noble 1 PlusPowder, dentifrice0.7 g/100gDentalHankuk Bowonbio Co., Ltd2012-11-30Not applicableUs
Noble G PlusPaste, dentifrice0.7 g/100gDentalHankuk Bowonbio Co., Ltd2012-11-30Not applicableUs
Trident Advantage GumGum, chewing364 mgDentalPfizer Canada Inc., Consumer Healthcare Division2000-03-272002-08-06Canada
Xylifresh 100 (peppermint) - Gum 827 mgGum, chewing827 mgDentalLeaf Healthcare, Inc.1996-12-311997-12-22Canada
Xylifresh 100 (spearmint) - GumGum, chewing827 mgDentalLeaf Healthcare, Inc.1996-12-311997-12-22Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Adea GargleXylitol (5 g/100mg) + Sodium bicarbonate (36.2 g/100mg)Tablet, chewableOralK2resource Co., Ltd.2018-03-012018-04-01Us
Adea GargleXylitol (5 g/100mg) + Sodium bicarbonate (36.2 g/100mg)Tablet, chewableOralK2resource Co., Ltd.2018-03-01Not applicableUs
Yumaki Original Mint ToothXylitol (0.1 g/100g) + Aminocaproic Acid (0.05 g/100g) + Ascorbic acid (0.005 g/100g) + Green tea leaf (0.1 g/100g) + Menthol (0.1 g/100g) + Peppermint oil (0.05 g/100g) + Water (45.15 g/100g)Paste, dentifriceTopicalJeno And Company2017-11-01Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Fluor-a-dayXylitol (236.79 mg/1) + Sodium fluoride (0.25 mg/1)Tablet, chewableOralArbor Pharmaceuticals2010-08-152014-09-30Us
Fluor-a-dayXylitol (236.79 mg/1) + Sodium fluoride (1 mg/1)Tablet, chewableOralArbor Pharmaceuticals2010-08-152014-10-31Us
Fluor-a-dayXylitol (236.79 mg/1) + Sodium fluoride (0.5 mg/1)Tablet, chewableOralArbor Pharmaceuticals2010-08-152014-10-31Us
Categories
UNII
VCQ006KQ1E
CAS number
87-99-0
Weight
Average: 152.1458
Monoisotopic: 152.068473494
Chemical Formula
C5H12O5
InChI Key
HEBKCHPVOIAQTA-SCDXWVJYSA-N
InChI
InChI=1S/C5H12O5/c6-1-3(8)5(10)4(9)2-7/h3-10H,1-2H2/t3-,4+,5+
IUPAC Name
(2R,3r,4S)-pentane-1,2,3,4,5-pentol
SMILES
OC[C@H](O)[C@@H](O)[C@H](O)CO

Pharmacology

Indication

Indicated for use as a sugar substitute, and oral hygiene active ingredient.

Pharmacodynamics

There has been evidence of xylitol in dental hygiene in reducing dental caries disease and also reversing the process of early caries [1]. Xylitol increases salivary flow and pH, reduces the levels of Streptococcus mutans in plaque and saliva and reduces the adhesion on the microorganism to the teeth surface [1]. Streptococcus mutans is the main target plaque microorganism [2], but xylitol may potentially have inhibitory actions against several other bacterial species [1]. It prevents a shift of the bacterial community towards a more cariogenic microflora in oral environment [4]. Oral ingestion of xylitol causes a smaller rise in plasma glucose and insulin concentrations than does the ingestion of glucose in healthy men and diabetics [6].

Mechanism of action

Xylitol is initially taken up by the microorganism and accumulates intracellularly. Accumulated xylitol is transported into an energy-consuming cycle, or the inducible fructose transport system. It is converted to non-metabolizable, toxic xylitol-5-phosphate via phosphoenolpyruvate: a constitutive fructose phosphotransferase system by S. mutans [1]. This metabolic process of xylitol, without the gain of any energy molecules, results in the development of intracellular vacuoles and cell membrane degradation. S. mutans dephosphorylates xylitol-5-phosphate and expels it from the cell, in which requires energy consumption. This ultimately leading to starving of microorganism and growth inhibition [1]. Long-term exposure to xylitol can cause microorganisms to develop resistance to xylitol. This clinically beneficial selection process creates xylitol-resistant mutans strains that are less virulent and less cariogenic than their parent strains [3]. Xylitol also increases the concentrations of ammonia and amino acids in plaque, thereby neutralizing plaque acids [1]. A study suggests that xylitol may also promote remineralization of deeper layers of demineralized enamel by facilitating Ca2+ and phosphate movement and accessibility [5].

TargetActionsOrganism
UXylose isomeraseNot AvailableArthrobacter sp. (strain NRRL B3728)
UXylose isomeraseNot AvailableStreptomyces rubiginosus
UXylose isomeraseNot AvailableStreptomyces olivochromogenes
UXylose isomeraseNot AvailableActinoplanes missouriensis (strain ATCC 14538 / DSM 43046 / CBS 188.64 / JCM 3121 / NCIMB 12654 / NBRC 102363 / 431)
UHyaluronate lyaseNot AvailableStreptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
Absorption

Xylitol is absorbed in the small intestine via passive diffusion with a slow absorption rate [1].

Volume of distribution

No pharmacokinetic data available.

Protein binding

No pharmacokinetic data available.

Metabolism

In mammals, xylitol is mainly metabolized in the liver where it is oxidized to D-xylulose by xylitol dehydrogenase and cofactor NAD. D-xyluose is further phosphorylated and metabolized by xylulose kinase to xylulose 5-phosphate (Xu5P), an intermediate of the nonoxidative branch of the pentose phosphate pathway [6]. Xu5P is reported to activate nuclear transport and the DNA-binding activities of carbohydrate response element binding protein (ChREBP) via activation of activation of protein phosphatase 2A (PP2A) in vitro [6]. Activation of ChREBP thereby upregulates the gene transcription of lipogenic enzymes in vitro, which may stimulate lipogenesis in the liver [6].

Route of elimination

No pharmacokinetic data available.

Half life

No pharmacokinetic data available.

Clearance

No pharmacokinetic data available.

Toxicity

Oral LD50 is 16500 mg/kg in rat [MSDS]. At high dosages, xylitol can cause diarrhea in children at 45 g/d and 100 g/d in adults [1].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Nayak PA, Nayak UA, Khandelwal V: The effect of xylitol on dental caries and oral flora. Clin Cosmet Investig Dent. 2014 Nov 10;6:89-94. doi: 10.2147/CCIDE.S55761. eCollection 2014. [PubMed:25422590]
  2. Soderling E, Hirvonen A, Karjalainen S, Fontana M, Catt D, Seppa L: The effect of xylitol on the composition of the oral flora: a pilot study. Eur J Dent. 2011 Jan;5(1):24-31. [PubMed:21311610]
  3. Trahan L, Bourgeau G, Breton R: Emergence of multiple xylitol-resistant (fructose PTS-) mutants from human isolates of mutans streptococci during growth on dietary sugars in the presence of xylitol. J Dent Res. 1996 Nov;75(11):1892-900. doi: 10.1177/00220345960750111201. [PubMed:9003237]
  4. Trahan L: Xylitol: a review of its action on mutans streptococci and dental plaque--its clinical significance. Int Dent J. 1995 Feb;45(1 Suppl 1):77-92. [PubMed:7607748]
  5. Miake Y, Saeki Y, Takahashi M, Yanagisawa T: Remineralization effects of xylitol on demineralized enamel. J Electron Microsc (Tokyo). 2003;52(5):471-6. [PubMed:14700079]
  6. Amo K, Arai H, Uebanso T, Fukaya M, Koganei M, Sasaki H, Yamamoto H, Taketani Y, Takeda E: Effects of xylitol on metabolic parameters and visceral fat accumulation. J Clin Biochem Nutr. 2011 Jul;49(1):1-7. doi: 10.3164/jcbn.10-111. Epub 2011 Jun 17. [PubMed:21765599]
External Links
KEGG Drug
D00061
KEGG Compound
C00379
PubChem Substance
347911150
ChemSpider
6646
ChEBI
17151
ChEMBL
CHEMBL96783
HET
XYL
Wikipedia
Xylitol
PDB Entries
1fx5 / 1lte / 1njr / 1s5n / 1w3y / 1xig / 1xim / 1xin / 1xlc / 1xld
show 20 more
MSDS
Download (33.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedOtherCystic Fibrosis (CF)1
1, 2CompletedTreatmentCystic Fibrosis (CF)1
2Active Not RecruitingTreatmentChronic Rhinosinusitis / Persian Gulf Syndrome / Sinusitis, Acute / Tiredness1
2CompletedSupportive CareOral Mucositis1
2, 3Not Yet RecruitingTreatmentChronic Rhinosinusitis1
2, 3RecruitingPreventionDental Plaque1
4CompletedPreventionDental Caries and Streptococcus Mutans Count1
Not AvailableCompletedTreatmentChronic Rhinosinusitis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Paste, dentifriceDental0.07 g/100g
Tablet, chewableOral
Powder, dentifriceDental0.7 g/100g
Paste, dentifriceDental0.7 g/100g
Gum, chewingDental364 mg
Gum, chewingDental827 mg
Paste, dentifriceTopical
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)92-96MSDS
boiling point (°C)215-217MSDS
Predicted Properties
PropertyValueSource
Water Solubility664.0 mg/mLALOGPS
logP-2.5ALOGPS
logP-3.1ChemAxon
logS0.64ALOGPS
pKa (Strongest Acidic)12.76ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area101.15 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity32.44 m3·mol-1ChemAxon
Polarizability14.42 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6885
Blood Brain Barrier-0.6671
Caco-2 permeable-0.8777
P-glycoprotein substrateNon-substrate0.6813
P-glycoprotein inhibitor INon-inhibitor0.9518
P-glycoprotein inhibitor IINon-inhibitor0.9247
Renal organic cation transporterNon-inhibitor0.9142
CYP450 2C9 substrateNon-substrate0.8802
CYP450 2D6 substrateNon-substrate0.8706
CYP450 3A4 substrateNon-substrate0.7419
CYP450 1A2 substrateNon-inhibitor0.8471
CYP450 2C9 inhibitorNon-inhibitor0.9326
CYP450 2D6 inhibitorNon-inhibitor0.9343
CYP450 2C19 inhibitorNon-inhibitor0.9169
CYP450 3A4 inhibitorNon-inhibitor0.9519
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9681
Ames testNon AMES toxic0.8869
CarcinogenicityNon-carcinogens0.7794
BiodegradationReady biodegradable0.8084
Rat acute toxicity0.9961 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9571
hERG inhibition (predictor II)Non-inhibitor0.9235
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0gb9-0983000000-a3ba95772bec5304c32d
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-0gba-0940000000-64e78d1e92fe9d145937
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as sugar alcohols. These are hydrogenated forms of carbohydrate in which the carbonyl group (aldehyde or ketone, reducing sugar) has been reduced to a primary or secondary hydroxyl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Sugar alcohols
Alternative Parents
Monosaccharides / Secondary alcohols / Polyols / Primary alcohols / Hydrocarbon derivatives
Substituents
Sugar alcohol / Monosaccharide / Secondary alcohol / Polyol / Hydrocarbon derivative / Primary alcohol / Alcohol / Aliphatic acyclic compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
pentitol (CHEBI:17151)

Targets

Kind
Protein
Organism
Arthrobacter sp. (strain NRRL B3728)
Pharmacological action
Unknown
General Function
Xylose isomerase activity
Specific Function
Not Available
Gene Name
xylA
Uniprot ID
P12070
Uniprot Name
Xylose isomerase
Molecular Weight
43291.15 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Streptomyces rubiginosus
Pharmacological action
Unknown
General Function
Xylose isomerase activity
Specific Function
Involved in D-xylose catabolism.
Gene Name
xylA
Uniprot ID
P24300
Uniprot Name
Xylose isomerase
Molecular Weight
43226.915 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Streptomyces olivochromogenes
Pharmacological action
Unknown
General Function
Xylose isomerase activity
Specific Function
Involved in D-xylose catabolism.
Gene Name
xylA
Uniprot ID
P15587
Uniprot Name
Xylose isomerase
Molecular Weight
42922.7 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Actinoplanes missouriensis (strain ATCC 14538 / DSM 43046 / CBS 188.64 / JCM 3121 / NCIMB 12654 / NBRC 102363 / 431)
Pharmacological action
Unknown
General Function
Xylose isomerase activity
Specific Function
Not Available
Gene Name
xylA
Uniprot ID
P12851
Uniprot Name
Xylose isomerase
Molecular Weight
43498.425 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
Pharmacological action
Unknown
General Function
Hyaluronate lyase activity
Specific Function
Not Available
Gene Name
Not Available
Uniprot ID
Q54873
Uniprot Name
Hyaluronate lyase
Molecular Weight
120770.645 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]

Drug created on December 03, 2015 09:51 / Updated on November 02, 2018 07:07